Therapeutic irradiation is commonly used in the management of intracranial neoplasia in humans, and has associated with it a potential for normal tissue damage which may be life threatening. Increasing use of combined modality treatments, radiosensitizer compounds, hyperthermia and high LET radiations may increase the likelihood of adverse effects of irradiation. The risks associated with currently used time-dose-fractionation schemes or with new or more aggressive treatments are not clearly defined. A suitable animal model, characterized by similar morphologic, physiologic and pathologic changes after irradiation to those observed in man would be helpful in the establishment of such risk estimates. The overall objective of this proposal is to study the effects of radiation on the normal canine brain. Quantitative computed tomography (QCT) techniques will be used to noninvasively evalute changes induced by single and multifraction doses of megavoltage x-irradiation. Pre-contrast and post-contrast densitometry, dynamic flow related studies, contrast washout evaluation and quanititative volume analyses will be used to assess the morphologic and functional aspects of late radiation lesions in the brain as a function of time after irradiation. QCT parameters will be determined for various regions of the brain and correlated with histopathologic findings. Quantitative endpoints will be expressed in terms of dose response and time effect relationships. The noninvasive character and precision provided QCT techniques, the capability to do repeated studies in the same animal, and the multiplicity of endpoints provide a large and sensitive data base from which quantitative information can be derived concerning the devlopment of radiation-induced late brain damage. The various endpoints, dose response and time response relationships that will be determined in this study can be used to compare different dose regimens, fractionation schemes, combined modality treatments and radiation types in terms of late damage in the brain. This type of information will be useful in establishing optimal protocols for the treatment of intracranial tumors in man.